毒性化學物質 資料多取自Lab safety series

Toxic Chemical Hazards All chemicals can be toxic, but few actually hurt us. WHY? It’s the dose that makes the poison

討論重點 劑量與效應 接觸途徑 預防之道 毒性化學物管理法 (環保署); 作業環境檢測 (勞委會)

取自工業安全科技1993.10.1

The higher the dose of a chemical, the more severe the response Dose-Response Model The higher the dose of a chemical, the more severe the response

Dose-Response Model 劑量通常受到下列因素影響: 物質的相對毒性 濃度 接觸時間 (應該也包括進入人體的方式，以及進入的速度)

劑量與效應多半遵循高斯分佈

Relative Toxicity Some chemicals are more toxic than others at the same quantity, so toxicity indexes were developed

LD50 Refers to dose fed to an animal population The lethal dose to 50% of an animal population Given in mg/kg of body weight(應該報導試驗的動物)

LC50 Refers to the concentration of chemical in the air inhaled by an animal population The lethal concentration to 50% of an animal population Given in mg/m3 (注意單位)

LD50 & LC50 Remember that these are lethal doses to animals, not people Still the best method for relative toxicity

以劑量言: LD50 (lethal) > TD50 (toxic) > ED50 (effective) > ED10

* 毒性效應一定會因人而異，所以存在標準偏差 From Crowl & Louvar

TLV The Threshold Limit Value (TLV) is a guideline concentration developed by the American Council of Governmental Industrial Hygienists (ACGIH) TLVs are recommendations and should be used as guidelines for good practices也就是我國作業環境容許濃度之參考基準

TLV TLVs refer to airborne concentrations of substances TLVs represent conditions under which it is believed that nearly all workers may be repeatedly exposed to day after day without adverse health effects

TLV TLVs are based on available information from: industrial experience experimental human studies experimental animal studies The amount and nature of the information varies from substance to substance ; consequently, the precision of the estimated TLV is also subject to variation

TLV-TWA Threshold Limit Value-Time Weighted Average The time-weighted average concentration for a normal 8-hour workday and a 40-hour workweek Nearly all workers may be repeatedly exposed, day after day, without adverse effect TWA = 1/8 C(t) dt (t: 0  tw) where tw= worker shift time in hours

TLV-STEL irritation chronic or irreversible tissue damage Threshold Limit Value-Short Term Exposure Limit The concentrations to which workers can be exposed continuously for a short period of time without suffering from: irritation chronic or irreversible tissue damage narcosis of sufficient degree to increase the likelihood of accidental injury, impair self-rescue, or materially reduce work efficiency

Ceiling Limit The concentration that should not be exceeded during any part of the working exposure

Short Term Exposure Limit STEL Short Term Exposure Limit A 15 minute TWA exposure which should not be exceeded at any time during a workday even if the 8 hour TWA is within the TLV-TWA Exposures above the TLV-TWA up to the STEL should not be longer than 15 minutes and should not occur more than four times per day

STEL There should be at least 60 minutes between successive exposures in this range Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day Under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded

Permissible Exposure Limit PEL Permissible Exposure Limit PEL is an exposure limit set by OSHA Similar to TLVs, the PEL refers to concentrations to which the employee may be exposed PELs are legally binding

IDLH Immediately Dangerous to Life or Health Specifically refers to the acute respiratory exposure that poses an immediate threat of loss of life, immediate or delayed irreversible adverse effects on health, or acute eye exposure that would prevent escape from a hazardous atmosphere

Relative Toxicity The LD50, LC50, TLV, PEL, STEL, Ceiling, and IDLH provide a good index of the toxicity of the chemical

不同的毒性物質，其效應各有特色。圖中顯示A在高劑量時比B毒性為強。

相對毒性 以LD50區分 * 高毒性: LD50 < 500 mg/Kg; * 毒性: 500 < LD50 < 5000 以劑量區分 (LC50 x exposure time) * 高毒性: 劑量 <500 * 毒性: 500 < 劑量 < 5,000 * 輕毒性: 5,000 < 劑量 < 50,000 * 稀毒性: 50,000 < 劑量 < 150,000

Concentration The higher the concentration or dose of the chemical, the higher the risk of harmful effects Nitrogen at 78% concentration in the air is healthy, but at over 85%, it asphyxiates humans

Probable Oral Dose for Humans Concentration Probable Oral Dose for Humans Toxicity Rating Dose For Average Adult Practically nontoxic >15 g/kg more than 1 quart Slightly toxic 5-15 g/kg between pint and quart Moderately toxic .5-5 g/kg between ounce and pint Very toxic 50-500 mg/kg between tsp. and ounce Extremely toxic 1-50 mg/kg between 7 drips and tsp. Super toxic <1 mg/kg a taste

Time of Exposure The dose-response model teaches the toxicity risk increases as: relative toxicity increases concentration increases length of exposure increases

Effects Acute Chronic Latency Period a rapid, sudden exposure the harmful effects are immediate Chronic repeated, small exposures the harmful effects are delayed sometimes as long as 40 years Latency Period the time between the exposure and the effect

Probit Probit = probability unit 是一種表示response-dose關係的方法，可以畫成直線圖，方便比較。 P probability = {1/(2) 1/2}  exp(-u2/2) du [from Y-5 to -] 提供P 與probit變數Y間的關係 Y = k1 + k2 lnV; k1, k2是參數，V代表劑量dose (caustic factor); Y probit variable; k1, k2則視意外事件之不同而有差別。

本圖協助將probit轉換為百分率

若干常用有機溶劑的毒性 確定有害者: benzene, carbon bisulfide, CCl4, formaldehyde, methyl alcohol, phenol, tetrachloroethane, etc. 中等危害性: amyl acetate, cumene, butyl alcohol, cycloheptane, nitroethane, toluene, xylent, etc. 比較無害者: ethyl alcohol, ethyl acetate, ethyl ether, heptane, hexane, petroleum ether, etc.

How do chemicals enter our bodies to cause harm? ROUTES OF ENTRY How do chemicals enter our bodies to cause harm?

Routes of Entry Four routes of entry are recognized: Inhalation 吸入 Absorption 吸收(皮膚) Ingestion 食入(消化器官) Injection 注射  劑量過高的結果, 中毒或職業病

Inhalation Inhalation is the most common form of occupational exposure to chemicals

Inhalation Minimize inhalation of hazardous chemicals through: good ventilation use of fume hoods/glove-box respirator Always try to engineer out the hazard BEFORE resorting to a respirator

Inhalation Respirators can pose additional hazards to the user Punctured eardrums also provide an inhalation route of entry

Absorption The most frequently reported occupational injuries are chemical effects to the skin

Absorption Not all chemicals are absorbed through the skin: many defat the skin and cause injury How do we minimize chemical absorption through the skin? Gloves provide a good barrier when the appropriate glove materials are used

Ingestion We probably do not eat our lab chemicals so how do we sometimes swallow them?

Ingestion NO eating or drinking in the lab NO smoking in the lab Minimize the ingestion route of entry by: NO eating or drinking in the lab NO smoking in the lab ALWAYS wash your hands when leaving the lab

Injection Very few, if any, accidents occur in the laboratory as a result of accidental injection of a chemical filled syringe

Injection How can this happen? cleaning up contaminated broken glass cutting self on contaminated sharps leak in high pressure hoses puncturing self with a contaminated syringe

Injection How can this route of entry be minimized? use only a broom and dust pan for cleaning up broken glass dispose of used syringes, do not recap them wear puncture resistant gloves

人體吸收速率以及吸收量，會因為接觸方式不同而異。

途徑: 進入人體  組織吸收  血液傳佈  生物轉化  附著於器官或組織; 藉由新陳代謝排除

幾種劑量的概念 曝露劑量(exposure dose): 環境中毒性化學物質的量 潛在劑量(potential dose): 被人體吸入的量 應用劑量(applied dose): 真正到達肺部或腸胃的量 內在劑量(internal dose): 被吸收進入血液內的量 生化有效劑量(biologically effective dose): 到達器官或組織的量

攝 入 率 Intake Rate = 曝露濃度 x 吸入率 吸入率 (經由皮膚，眼睛，肺部等) = f(滲透係數，吸收係數，表面積)

人體的反應 不可逆的反應: 致癌(carcinogen)，基因受損(mutagen)，生殖能力受損(reproductive hazard)，畸胎(teratogen) 可逆(可復原)的反應: 皮膚，肝臟，血液，腎臟，神經系統，肺部等

化學物質的生物指標 Biological exposure indices: BEI 例如量測尿液中的丙酮含量,血液中的重金屬含量,呼出空氣中的正己烷含量等 可以用於配合作業環境測定,更具參考價值 一般影響生物指標的因素包括: * 被評估者的生理及健康狀態 * 職業暴露環境 * 環境暴露來源: 住家,飲水,食物等 * 個人生活習慣: 菸酒,藥物 * 評估方法的嚴謹性: 採樣及分析技術

以下介紹幾種簡易的方法期望減低毒性物質的風險 SUMMARY 以下介紹幾種簡易的方法期望減低毒性物質的風險

SUMMARY If the toxicity of a chemical is unknown, treat it as toxic

SUMMARY Use a fume hood or glove box when the chemical could become a vapor or dust

SUMMARY Always wear the proper personal protective equipment eye protection gloves lab coat

Change protective garments as required SUMMARY Change protective garments as required

SUMMARY Decontaminate before eating, drinking, smoking, or going to the bathroom

Minimize the time of exposure SUMMARY Minimize the time of exposure

SUMMARY Become familiar with the Standard Operating Procedures for safe handling of toxic materials

Toxics Knowledge of a chemical’s toxic properties and the correct handling precautions can prevent adverse health effects (e.g. read MSDS)